Tacrolimus, a calcineurin inhibitor widely used in clinical practice, is associated with chronic nephrotoxicity, particularly under conditions of reduced renal reserve. However, experimental models that efficiently reproduce tacrolimus-accelerated renal injury within a short time frame remain limited. In this study, we established an in vivo model to evaluate tacrolimus-associated renal injury using subtotal (5/6) nephrectomized rats. Low-dose tacrolimus was administered for two weeks starting four weeks after surgery, and the effects of concomitant everolimus treatment were examined as a pharmacological modulator. Renal function was assessed by plasma creatinine and urinary albumin parameters, and renal injury was evaluated by histological analyses and protein expression profiling. Tacrolimus administration significantly exacerbated renal dysfunction and structural injury in nephrectomized rats, as evidenced by increased plasma creatinine levels, albuminuria, and enhanced interstitial fibrosis. Concomitant everolimus treatment was associated with partial attenuation of these functional and histopathological changes. The present study demonstrates the establishment of a tacrolimus-accelerated renal injury model under conditions of reduced renal reserve. Everolimus co-treatment was associated with partial attenuation of renal injury under the experimental conditions used.
Nakayama et al. (Tue,) studied this question.